Related Experiment Video
Updated: Sep 21, 2026
Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
Published on: December 22, 2023
Acute p38 MAPK activation decreases force development in ventricular myocytes
Yi Chen1, Ravi Rajashree, Qinghang Liu
1Department of Physiology, University of Tennessee Health Sciences Center, 894 Union Ave., Memphis, TN 38163, USA.
Abstract:
Evidence suggests that p38 mitogen-activated protein kinase (MAPK) activation influences cardiac function on an acute basis. The characterization and mechanisms by which this occurs were investigated in the present study. Adult rat ventricular myocytes treated with 1 mM arsenite for 30 min had a 16-fold increase in p38 MAPK phosphorylation that was attenuated by SB-203580 (a p38 MAPK inhibitor). Extracellular signal-regulated protein kinase (ERK) and c-Jun NH2-terminal kinase (JNK) were also minimally activated, but this activation was not sensitive to SB-203580. In addition, arsenite caused a p38 MAPK-independent translocation/activation of protein phosphatase 2a (PP2a) and decrease in phosphorylation of myosin light chain 2 (LC2). Arsenite-p38 MAPK activation led to translocation of heat shock protein 27 but not alpha B-crystallin to the myofilaments. Using isolated cardiomyocytes, we determined that arsenite reduces isometric tension without a change in Ca2+ sensitivity of tension via p38 MAPK and lowers myofibrillar actomyosin Mg2+-ATPase activity in a p38 MAPK-independent manner. Thus arsenite induces a p38 MAPK-independent change in PP2a and LC2 that may account for the arsenite-dependent decrease in ATPase and a p38 MAPK-dependent modification of the myofilaments that decreases myocardial force development.
Insights
Arsenite exposure impacts heart muscle function through p38 mitogen-activated protein kinase (MAPK) and other pathways. This study reveals p38 MAPK-dependent and independent mechanisms affecting cardiac contractility and enzyme activity.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- p38 mitogen-activated protein kinase (MAPK) activation is implicated in acute cardiac function.
- Understanding the precise mechanisms of p38 MAPK in cardiac regulation is crucial.
Purpose of the Study:
- To investigate the mechanisms by which p38 MAPK activation influences cardiac function.
- To characterize the role of arsenite in modulating cardiac cellular processes.
Main Methods:
- Adult rat ventricular myocytes were treated with arsenite.
- p38 MAPK phosphorylation was measured and inhibited using SB-203580.
- Protein phosphatase 2a (PP2a) activation, myosin light chain 2 (LC2) phosphorylation, and heat shock protein translocation were assessed.
- Isometric tension and myofibrillar actomyosin Mg2+-ATPase activity were measured in isolated cardiomyocytes.
Main Results:
- Arsenite significantly increased p38 MAPK phosphorylation in a manner sensitive to SB-203580.
- Arsenite induced p38 MAPK-independent PP2a activation and decreased LC2 phosphorylation.
- Arsenite reduced isometric tension via p38 MAPK and lowered Mg2+-ATPase activity independently of p38 MAPK.
- p38 MAPK activation led to heat shock protein 27 translocation to myofilaments.
Conclusions:
- Arsenite affects cardiac function through both p38 MAPK-dependent and independent pathways.
- p38 MAPK-independent changes in PP2a and LC2 contribute to decreased ATPase activity.
- p38 MAPK-dependent myofilament modification leads to reduced myocardial force development.
